Histiocytic sarcoma

Definition

A malignant neoplasm of histiocytes, positive for one or more histiocytic markers but negative for accessory/dendritic cell markers. Many cases described in the past would now be classified as diffuse large B-cell lymphoma or anaplastic large cell lymphoma.

Synonyms

"True" histiocytic lymphoma, malignant histiocytosis (of the gastrointestinal tract).

Equivalent normal cell

Phagocytic cells may be freely mobile (monocytes) or reside in tissues (e.g. Kupffer cells). Their cytoplasm contains numerous vacuoles, lysosomes, mitochondria and residual bodies. There is immunoreactivity for lysozyme, a1-antitrypsin, CD68, CD11c, CD14 and CD1632.

Epidemiology

A rare tumour showing a wide age range including children but most common in adults. A few patients have a previous history of a mediastinal germ cell tumour.

Clinical features

One third of cases are nodal, one third cutaneous or deeper soft tissues and one third present at other extranodal sites, particularly the gastrointestinal tract2. Rare sites include spleen, bone marrow, nasal cavity5, lung5 and brain4. Patients may have fever, weight loss, a rash, or hepatosplenomegaly. Lytic bone lesions and pancytopenia are not uncommon. Some cases present as disseminated "malignant histiocytosis2. There is an association with other haematological disorders2. Patients may have a profound peripheral eosinophilia5.

Histopathology

In extranodal cases, the mass may be well circumscribed or infiltrating. Tumour cells are usually large with abundant eosinophilic cytoplasm, which may be foamy/xanthomatous. The cells may be focally spindled5. Nuclei are oval to irregular with vesicular chromatin and usually large eosinophilic nucleoli5. Nuclear atypia is variable. Multinucleate forms are common. Mitotic rates are very variable5. There may be haemophagocytosis2. Small lymphocytes, plasma cells, benign histiocytes and eosinophils are present in variable, often large, numbers. In lymph nodes, spleen and bone marrow, there is often sinusoidal involvement2. In the central nervous system, histiocytic lymphomas with a dense mixed inflammatory cell infiltrate and abscess formation have been reported; this inflammatory component may mask the underlying neoplasm1.

Immunohistochemistry; see the immunohistochemical differentiation of histiocytic and dendritic cell neoplasms

Immunoglobulin T cell antigen-receptor genes should be of germline configuration.

Ultrastructure

There are lysosomes. Birbeck granules, desmosomes and interdigitating junctions are absent.

Differential diagnosis

• Other histiocytic and dendritic cell neoplasms; see the immunohistochemical differentiation of histiocytic and dendritic cell neoplasms. Since some histiocytic sarcomas are positive for CD1a and S-100, only nuclear morphology or ultrastructure reliably differentiate.

• Differentiation from interdigitating dendritic cell sarcoma, which has an overlapping immunophenotype, may require electron microscopy2.

• Diffuse large B-cell lymphoma; lineage markers are necessary to distinguish.

• Anaplastic large cell lymphoma; CD30 and EMA positive. May also show a marked inflammatory cell infiltrate.

• Cutaneous involvement by monoblastic leukaemia; the immunophenotype and ultrastructure are similar but the cells are smaller and more monomorphic with intensely basophilic cytoplasm, show Indian file infiltration and have a higher mitotic count2. CD34 may be positive2.

• Metastatic malignant melanoma: some cases are positive for CD68, using either PG-M1 or KP1.

• Metastatic large cell carcinoma: renal cell carcinoma may look very similar and may be positive for CD68, using either PG-M1 or KP1.

Prognosis

Usually an aggressive neoplasm with a poor response to therapy and a poor prognosis2: some localised cases behave less agressively5. Metastases occur to lymph nodes, lung and bone5.

References

0World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1Cheuk, W., Walford, N., Lou, J., et al. Primary histiocytic lymphoma of the central nervous system: a neoplasm frequently overshadowed by a prominent inflammatory component. Am J Surg Pathol 2001;25:1372-1379.

2Pileri, S.A., Grogan, T.M., Harris, N.L., Banks, P., Campo, E., Chan, J.K., Favera, R.D., Delsol, G., De Wolf-Peeters, C., Falini, B., Gascoyne, R.D., Gaulard, P., Gatter, K.C., Isaacson, P.G., Jaffe, E.S., Kluin, P., Knowles, D.M., Mason, D.Y., Mori, S., Muller-Hermelink, H.K., Piris, M.A., Ralfkiaer, E., Stein, H., Su, I.J., Warnke, R.A. and Weiss, L.M. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002;41:1-29.

3Copie-Bergman, C., Wotherspoon, A.C., Norton, A.J., Diss, T.C. and Isaacson, P.G. True histiocytic lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases. Am J Surg Pathol 1998;22:1386-92.

4Sun, W., Nordberg, M.L. and Fowler, M.R. Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol 2003;27:258-65.

5Hornick, J. L., E. S. Jaffe, et al. (2004). "Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy." Am J Surg Pathol 28(9): 1133-44.

6 Sean K. Lau, Immunohistochemical Expression of Langerin in Langerhans Cell Histiocytosis and Non-Langerhans Cell Histiocytic Disorders AJSP 2008; 32:615

This page last revised 8.10.2004.

©SMUHT/PW Bishop